Individuals are frequently exposed to conditions that elevate internal temperature which results in increased cutaneous vascular conductance accompanied by significant fluid loss via sweating. It is common for individuals in this condition to have compromised blood pressure control evidenced by lightheadedness, vertigo, and nausea upon standing or similar gravitational stressors, which can lead to syncope and a high potential of injury. The objective of this proposal is to identify mechanisms responsible for attenuated blood pressure control leading to orthostatic intolerance during heat stress. Specific Aim 1: Tests the hypothesis that restoration of central blood volume (indexed by central venous pressure) during heat stress improves blood pressure control and orthostatic tolerance. Specifically the effects of volume restoration on: 1) the relationship between SV and pulmonary capillary wedge pressure (i.e., Frank-Starling curve), and 2) left ventricular end diastolic volume during gravitational stress, will be examined. Specific aim 2: Examine mechanisms of greater reductions in cerebral blood flow (CBF) during an orthostatic challenge while heat stressed. Specifically we will examine: 1) the role of decreased central venous pressure and cardiac output during combined heat and orthostatic stress on CBF, 2) the relative contributions of reduced arterial CO2 tensions (PaCO2) causing reduced CBF observed during heat stress and 3) the effect of heat stress on the sensitivity of the cerebral vasculature to changes in PaCO2 . These objectives will be accomplished by evaluating cardiovascular and hemodynamic variables during 1) normothermia, 2) heat stress, and 3) during heat stress + restoration of CBV via dextran/saline infusion. Some protocols will use lower body negative pressure to reduce CBV and thus mimic a state of hemorrhage. PUBLIC HEALTH RELEVANCE: Data obtained will provide important information regarding compromised blood pressure control during heat stress. Importantly, this will provide insight to those who treat individuals with an elevated internal temperature and particularly when this scenario is accompanied with a hemorrhagic injury. Such individuals may be soldiers fighting in conditions in which environmental temperature is elevated (e.g. Middle East), firefighters and police officers who serve in warmer climate locations, or any other incidents (e.g., car accident) in which an individual is profusely bleeding while at the same time their internal temperature is elevated.